Crizotinib


Concise Prescribing Info
Indications/Uses
ALK-positive locally advanced or metastatic non-small cell lung carcinoma.
Dosage/Direction for Use
Adult : PO 250 mg bid; may reduce dose, interrupt dosing, or discontinue based on individual safety and tolerability.
Dosage Details
Oral
Locally advanced non-small cell lung carcinoma, Metastatic non-small cell lung carcinoma
Adult: Anaplastic lymphoma kinase (ALK)-positive: 250 mg bid, given continuously until disease progression. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
Renal Impairment
CrCl (mL/min) Dosage
<30 (not requiring dialysis) Initially, 250 mg daily, if tolerated, gradually increase to 200 mg bid after at least 4 wk of treatment.
Hepatic Impairment
Severe: Contraindicated.
Administration
May be taken with or without food.
Contraindications
Congenital long QT syndrome. Severe hepatic impairment. Pregnancy and lactation.
Special Precautions
Patient w/ bradyarrhythmias, CHF, electrolyte abnormalities, risk for prolonged QT interval. Mild to moderate hepatic and severe renal (<30 mL/min, not requiring dialysis) impairment.
Adverse Reactions
Significant: Visual loss or impairment, photopsia, blurred vision, diplopia, vitreous floaters, photophobia, bradycardia, nausea and vomiting; severe neutropenia, lymphopenia, and thrombocytopenia.
Nervous: Dizziness, neuropathy, headache, insomnia, fatigue.
GI: Decreased appetite, dyspepsia, diarrhoea, constipation, oesophageal disorders, abdominal pain, stomatitis, dysgeusia.
Resp: Pulmonary embolism, upper resp tract infection, cough.
Hepatic: Increased liver transaminases.
Genitourinary: Increased creatinine, renal cyst.
Endocrine: Hypogonadism.
Musculoskeletal: Arthralgia.
Dermatologic: Rash.
Others: Oedema, fainting, hypophosphataemia, pain, fever.
Potentially Fatal: Hepatotoxicity, QTc prolongation, cardiac failure, GI perforation, interstitial lung disease/severe pneumonitis, hypoxia, acute resp distress syndrome, dyspnoea, empyema, pulmonary haemorrhage, renal failure (including acute cases).
Patient Counseling Information
This drug may cause vision disorder, symptomatic bradycardia or fatigue, if affected, do not drive or operate machinery.
MonitoringParameters
Monitor CBC, LFT, renal function, heart rate, BP, ECG and electrolytes; ophth evaluation. Assess pulmonary symptoms for interstitial lung disease or pneumonitis.
Drug Interactions
Plasma concentration is increased by potent CYP3A inhibitors (e.g. atazanavir, clarithromycin, indinavir, ketoconazole, saquinavir) and decreased by CYP3A inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifabutin, rifampicin). Increased risk of bradycardia w/ non-dihydropyridine Ca channel blockers, β-blockers, clonidine, digoxin, anticholinesterases, pilocarpine. Increased risk of torsades de pointes w/ QTc prolonging agents (e.g. disopyramide, quinidine, amiodarone, sotalol, cisapride).
Food Interaction
Increased plasma concentration w/ grapefruit or grapefruit juice. Reduced plasma concentration w/ St John’s wort.
Action
Description: Crizotinib, a tyrosine kinase inhibitor, selectively inhibits anaplastic lymphoma kinase (ALK). In patients w/ ALK-positive non-small cell lung carcinoma (NSCLC), the ALK gene is abnormally activated due to mutations or translocations, which may lead to the expression of oncogenic fusion protein which is responsible for tumour growth. Crizotinib inhibits ALK tyrosine kinase, thus reducing cellular proliferation and survival in tumours which express these fusion proteins. It also inhibits hepatocyte growth factor receptor (HGFR, c-MET), ROS1 (c-ros), and recepteur d’origine nantais (RON).
Pharmacokinetics:
Absorption: Bioavailability: 43%. Time to peak plasma concentration: 4-6 hr.
Distribution: Plasma protein binding: 91%.
Metabolism: Metabolised in the liver via oxidation (to form crizotinib lactam), and O-dealkylation by CYP3A4/5 enzymes.
Excretion: Via faeces (63%, 53% as unchanged drug); urine (22%, 2.3% as unchanged drug). Terminal elimination half-life: 42 hr.
Chemical Structure

Click on icon to see table/diagram/image
Storage
Store between 20-25°C.
This is a cytotoxic drug. Any unused portion should be disposed of in accordance with local requirements.
ATC Classification
L01XE16 - crizotinib ; Belongs to the class of protein kinase inhibitors, other antineoplastic agents. Used in the treatment of cancer.
Disclaimer: This information is independently developed by MIMS based on Crizotinib from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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